THE PREPARATION PROPERTIES 
AND USES OF 
SILICODUODECITUNGSTIC ACID 


BY 


EDWARD OSCAR NORTH 


B.S. Beloit College, 1018 
M.S. University of Illinois, 1922 


THESIS 


SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS 
FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY 
IN THE GRADUATE SCHOOL OF THE UNIVERSITY 
OF ILLINOIS, 1924 


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Reprinted from the JOURNAL OF THE AMERICAN PHARMACEUTICAL SOCIETY, 
Vol. XIII, Nos. 10 and 11, October and November, 1924 


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THE PREPARATION, PROPERTIES, ‘AND USES OF SILICO- 
DUODECITUNGSTIC ACID.* 


I. THE PREPARATION OF THE eACI DOAN hp oe sn a oa 
HISTORICAL, 


Silicoduodecitungstic? acid was discovered by Marignac (1) in 1863 while 
preparing ammonium tungstate. The acid was formed during extraction of tungs- 
ten from the ore, which contained silica, and, being extremely soluble, was found 
in the mother liquors. He then prepared the acid by boiling a mixture of tungstic 
acid with gelatinous silicic acid, obtaining the solid acid by evaporation of the 
filtered liquid. ‘The sodium, potassium, and ammonium salts were described, and 
the empirical formula SMO.20WO;.2SiO; suggested for the salts. In a second 
paper (2) in 1864 two other acids were described: tungstosilicic acid, an isomer of 
the first, to which the formula 12WO;.Si0:.4HO + Aq was given, and silico- 
decitungstic acid of the formula 9102.10WO;.4HO.3Aq. These acids were 
separated as mercurous salts, which were quite insoluble but easily decomposed 
by hydrochloric acid. 

Wyrouboff (3) in 1896 followed essentially the procedure of Marignac in pre- 
paring the acid, substituting nitric acid for hydrochloric in generating the tungstic 
acid. Copaux (4) in 1908 made one of the most valuable contributions to the 
knowledge of these compounds. ‘There were then three acids known, which, in 
modern nomenclature, had the formulas 


A. SiO».12W0O;.2H.0.31Aq 
B. > $i0..12WO3.2H20.22Aq 
Ca SiO2.10WOs3.2H20.3Aq 


isomers 


Copaux prepared ‘‘A’”’ in three ways. 


1. By reaction in a boiling solution of sodium tungstate, Na,WO,, and sodium silicate, 
Na.SiO; (water glass), the solution being kept neutral with nitric acid. The Pompeu was ex- 
tracted by ether in the presence of sulfuric acid. 

2. By reaction between sodium tungstate and sodium orthosilicate, Na,SiOu, in a sealed 
tube at 150° C. The compound was isolated by means of ether and sulfuric acid. 

3. By reaction between boiling solutions of sodium tungstate and water glass made 
acid with acetic acid. ‘The compound was extracted as before. 

Acid ““B’’ was made by Procedure 3 under Acid “A,” with the substitution of sulphuric 
acid for the acetic acid. Acid ‘‘C’’ was formed by boiling ‘‘A”’ with a large excess of ammonia. 
Silica at first precipitated but almost completely redissolved and the ammonium salt of “C” 
crystallized from the filtrate. 


* Contribution from the Department of Chemistry of the University of Illinois. 

1 Read at the 72nd Meeting of the American Pharmaceutical Association, Buffalo, New 
York, August 25-29, 1924. 

2 Throughout this paper the term silicotungstic acid will be understood to refer to 
silicoduodecitungstic acid. 


6 


Goddefroy (5), 1876, found ‘that the alkaloidal salts of this acid were very 
insoluble, and also called attention. to the low solubility of the rubidium and 
caesium salts. Bertrand (6, 7), 1899) published the first detailed study of the alka- 
loidal salts of the acid.. He maintained that the paper of Goddefroy had not been 
available and was unknown to him, and that his study was entirely independent. 
He determined the sensitiveness of the reaction with eighteen or more alkaloids and, 
with Javillier (8, 9), used the acid in the quantitative determination of nicotine as 
a means of separating the pure alkaloid. Javillier (10) continued the work, study- 
ing the compounds of antipyrine (11), atropine, conine, pyramidone and spar- 
teine. | 

Guillemard (12) in 1903 described the use of the acid in determining the animal 
bases in the urine, which he referred to as alkaloidal nitrogen. Chapin (13), 
in 1911, published a direct method for the determination of nicotine in tobacco 
extracts, precipitating nicotine silicotungstate which was filtered and ignited, 
the determination being based on the weight of silicotungstic anhydride ob- 
tained. 

_.Ferenz and David (14) used the acid for the separation of alkaloids from im- 
pure solutions; recovering the alkaloids by decomposition of their salts with sodium 
hydroxide and ether. Rasmusson (15), 1917, outlined a procedure for the analysis 
of belladonna, using a correction factor because of the solubility of atropine silico- 
tungstate. Taigner (16), 1919, in studying the salts of atropine, strychnine and 
cocaine, found that when dried at 120° they all had the same type formula, vz., 
12WO3.Si02.2H.O.4 alkaloid. This permitted a gravimetric determination of 
these alkaloids without ignition. Heiduschka and Wolff (17) have studied the 
ratio of alkaloid to silicotungstic acid in a number of salts, determining the condi- 
tions under which these salts are formed. Sindlinger and Mach (18), 1924, have 
described the determination of pyridine and nicotine. By making allowance for 
the solubility of the pyridine salt in dilute hydrochloric acid it has been possible 
to determine this base quantitatively, and by the use of selective solvents for the 
two salts to determine the percentage of each of the two bases in a mixture. 


THEORETICAL. 


t 

Of the three methods suggested by Copaux (loc. cit.) for the preparation of 
“A”’ the first yields the best results. The sealed tube method is cumbersome and 
not applicable to large amounts, and the acetic acid used in the third method at — 
times causes some reduction of the silicotungstic acid. In the first method, there 
are at least several sources of difficulties. The sodium tungstate solution must be 
continuously stirred during the neutralization with nitric acid, since a local excess 
produces a precipitate of tungstic anhydride which dissolves with difficulty. The 
water glass, if not neutralized cautiously, yields a troublesome gel. During the 
heating the reaction of the solution must be frequently determined and nitric acid 
cautiously added to maintain neutrality. | 

Sulphuric acid is added in this method to finally liberate the acid, which is 
extracted by shaking the solution with ether. The ether solution is apparently 
similar to a hydrate, and is a heavy oily liquid, miscible neither with water nor 
ether. The sulphuric acid has a tendency to cause a precipitation of tungstic an- 
hydride which is carried down with the ether and promotes the formation of emul- 


fi 


sions. Sulphuric acid is carried down by the ether complex, cannot be volatilized 
with the ether, and tends to initiate a spontaneous decomposition on standing. 

In the procedure which we have adopted, hydrochloric acid is substituted for 
the nitric, sulphuric and acetic acids made use of by Copaux. ‘The formation of 
the acid from sodium tungstate and sodium silicate may be represented by the 
following reaction: 


12Na,WO, + NassiO; + 17H,O = 4H20.Si0..12WO; + 26NaOH 


If the reaction is to proceed from left to right it is only necessary to heat the acid 
to favor hydrolysis of the salts and to neutralize the alkali as it is set free. A slight 
theoretical excess of sodium silicate over sodium tungstate is used, and upon the 
slow addition of hydrochloric acid no tungstic anhydride is precipitated. ‘The only 
turbidity results from the liberation of the excess of silicic acid after the combina- 
tion has taken place, and this gel is readily removed by filtration. Addition of a 
large excess of hydrochloric acid does not produce a precipitate. After the reaction 
is complete, the silicotungstic acid is readily extracted by ether without emulsifica- 
tion forming a distinct bottom layer, and the hydrochloric acid carried down with 
the complex volatilizes with the ether. 

Previous investigators have been well agreed upon all of the properties of this 
acid except its basicity. Silicotungstic acid is quite stable. It will decompose 
chlorides and nitrates and is very resistant towards boiling sulphuric and perchloric 
acids. It is readily reduced by free metals such as copper, iron, aluminum and 
zinc, blue compounds being formed. 

Silicotungstic acid forms salts with mono-, di- and trivalent metals, but not 
with metals forming the oxide RO», according to Wyrouboff (loc. cit.). The salts 
may contain four or eight equivalents of the base. ‘Those which are of the nature 
of acid salts are very soluble in ether, alcohol and water, the neutral salts much 
less readily so. 

The most interesting property of the acid is that of forming sparingly soluble 
compounds with many organic bases. ‘These include the secondary and tertiary 
aliphatic and aromatic amines and quaternary ammonium derivatives. Insoluble 
salts are not formed by the primary amines. Salts of the secondary bases are 
usually soluble in hot water, those of the tertiary bases being least soluble. An ex- 
ception to the last statement is found in the effect of adjacent groups, such as the 
hydroxy! or carboxyl, which tend to neutralize the basicity. of the compound or to 
render its salts more soluble. 

Marignac (2) believed that the acid was octabasic. He found that a solution 
of a salt containing four equivalents of a base would decompose carbonates and 
turn blue litmus red. ‘The addition of more base turned the litmus blue, but on 
standing the red color returned. He also found that the acid was slowly decomposed 
by an excess of alkali with the formation of normal tungstate and silicate. 

When silicotungstic acid is titrated with standard alkali, using methyl orange 
as indicator, an end-point is obtained when the equivalent of four acid hydrogens 
have been neutralized. When the acid is titrated in hot solution with standard 
alkali and phenolphthalein indicator, the equivalent of twenty-six hydrogens are 
neutralized. Copaux (19) claimed that a sharp, though not permanent, end-point, 
was obtained with phenolphthalein at a point corresponding to the neutralization 


8 


of four hydrogens. ‘This is entirely contrary to results obtained in this laboratory. 

While the acid has been found to contain eight replaceable hydrogens, as shown 
by the formation of normal potassium and ammonium salts, the salts which are 
formed with tertiary organic bases represent the neutralization of but four eqtiva- 
lents of hydrogen. ‘The empirical formulas obtained upon analysis of these salts, 
however, do not support the theory of the octabasicity of the acid. In the usual 
manner of formation of such salts, there is a direct addition of the ions of the acid 
to the nitrogen of the base. Such an addition would mean that the number of 
molecules of water which must be eliminated to form the anhydride of the acid, 
would be the same, regardless of whether the acid or the alkaloidal salt was heated. 
Actual experiments show that only one-half as much water can be eliminated 
from the alkaloidal salt as from the free acid, forming the same anhydride in each 
ease. 

The neutral metallic salts were formed by the addition of an actual excess 
of alkali to the acid, the alkaloidal salts were precipitated in solutions acid with a 
strong mineral acid. It would thus appear that there is a condition of equilibrium 
existing in the acid solution, in which system there are both tetra- and octabasic 
acids present as members. The presence of a strong acid may repress the ioniza- 
tion of four hydrogens, permitting, at the same time, a dehydration with the forma- 
tion of a partial anhydride. ‘The condition is thus exactly the same as the state of 
equilibrium between chromic and dichromic acids, or between a dichromate and 
a true acid chromate in solution. 

The octapotassium salt, prepared in this laboratory, is acidic towards phenol- 
phthalein, neutral towards litmus, and alkaline towards methyl orange and methyl 
red. . 

The following is suggested as a structural formula for silicoduodecitungstic 
acid, showing it as a derivative of orthosilicic acid: 


W 
oF Ov On No 
HO 0 RS O OH 
\w LON ee Uo 
>w—0-si-0—w 
ORO i ee cag 
HO” No <i 0% oH 
O BSE O 
NN NA 
GE NS Bee vars 


One would predict that in an acid of this type, four hydrogens would have 
practically equal value and would be replaced simultaneously by a base in the 
neutralization of the acid. The ionization of the four remaining hydrogens would 
be of a much lesser degree. Copaux states that the remaining hydroxyl groups 
are alcoholic. However, neutral metallic salts are formed by the replacement 
of the eight hydrogens by bases, and a titration with a base using phenolphthalein 
as indicator shows a gradual endpoint which would be suggestive of a formula of 
this type. 


9 


Rosenheim and Jaenicke (20) reported that the acid formed quadratic crystals 
with twenty-eight molecules of water and rhombohedral crystals with twenty- 
two molecules of water. By the use of a dilatometer, they found the transition 
pointsat 2s.5.. y 

Copaux (4) claimed that his acids had, respectively, thirty-one and twenty- 
two molecules of water of crystallization. 

Another compound with fifteen molecules of water of crystallization was ob- 
tained. All of these forms effloresce rapidly and are therefore indefinite in compo- 
sition as kept in the laboratory. 

The product described in this paper is a white crystalline powder having the 
formula 4H20.Si02.12WO3.5H20. It is completely and rapidly soluble in water, 
ether, ethyl and other alcohols, acetone, ethyl acetate, and amyl acetate. The 
water of crystallization is very constant. A sample kept for a period of one year 
shows the same amount of water of crystallization. The solutions of the acid are 
very stable. The solid acid is very easy to handle, does not effloresce nor deli- 
quesce during weighing and is not reduced by contact with metals. 


EXPERIMENTAL. 


Preparation of Silicotungstic Acid.—One thousand grams of sodium tungstate were dis- 
solved in 2000 cc. of water. ‘To the solution were added 75 grams of a 40° Bé. solution of sodium 
silicate (water glass). The mixture was stirred briskly with a motor stirrer and heated to boiling, 
while 600 cc. of hydrochloric acid, d. 1.18, were added dropwise from a separatory funnel. The 
entire time consumed was about ninety minutes. The slight precipitate of gelatinous silicic acid 
was filtered off and the mixture cooled. Four hundred cc. of the concentrated hydrochloric acid 
were added and the solution cooled again. This solution in 500-cc. portions was shaken with ether 
and the bottom oily layer of the ether complex was drawn off. This was gently heated on the 
-steam-bath to. remove most of the ether, and the product finally dried in a vacuum oven at 70°. 
The mixture was stirred repeatedly during the drying on the steam-bath to break up lumps, and 
was not placed in the oven until it could be ground ina mortar. An 85% yield was obtained. 

Analysis of the Acid.—-Separation of the tungsten and silica was effected by the method 
.of Perillon (22), wherein the WO; was volatilized in a current of gaseous hydrochloric acid. The 
‘silica was then volatilized by means of hydrofluoric and sulfuric acids. The weight of silico- 
tungstic anhydride was determined by ignition of the acid. The tungsten as volatilized could 
not be readily collected, and its weight was therefore determined by difference. 


Theory for 
Found. 4H20.Si02.12W0O3.5H20. 
H,0 5.49% 5.55% 5.889% 
S102 2.04% 2.05% 1.996% 
wo; 92.46% 92.37% 92 615% 
SiO2:WOs::1 :11.76 1212 


Titration of Acid. Methyl Orange Indicator. 


Weight of sample 0.5024 gram 0.5217 gram 
Cc. N/1 KOH consumed 0.6699 0.6976 
Wt. equivalent to 1000 cc. N/1 KOH 750 .0 grams 747 .4 grams 
Equivalents per mole 4.008 4.02 

; Equivalent weight of anhydride, ave. 708 .4 
Theory FALCOF 


_ Titration of Acid. Phenolphthalein Indicator.—This titration was carried out in a boiling 
-solution, by adding standard potassium hydroxide solution until a permanent red color was ob- 
tained, then cooling the solution and titrating the excess of alkaliwith standard acid. 


10 


Weight of acid 0.5188 gram 0.5174 gram 
Cc. N/1 KOH 4.391 4.483 

Wt. equivalent to 1000 cc. N/1 KOH 118.1 grams 115.4 grams 
Equivalents per mole DO to 26 .0 

Theory 26.0 26.0 ; 


The reaction in this titration is the exact reverse of that previously given for 
the formation of the acid and is a substantiation of that reaction. ‘The silico- 
tungstic acid has been completely decomposed into potassium tungstate and po- 
tassium silicate, since the solution now gives a heavy precipitate with concentrated 
hydrochloric acid. If, however, the hydrochloric acid is titrated gradually into | 
the hot alkaline solution mentioned above, the silicotungstic acid is reformed. 


Preparation and Analysis of Potassium Silicutungstate.—This salt was prepared by adding 
a slight excess of potassium carbonate to a solution of the acid. The salt was recrystallized twice 
from hot water. ‘The water of crystallization was determined by igniting the salt. The silico- 
tungstic anhydride was determined by adding a solution of cinchonine hydrochloride to a solu- 
tion of the salt in dilute hydrochloric acid with ignition of the cinchonine silicotungstate pre- 
cipitated. The filtrate from this precipitate was evaporated with sulfuric acid and the residue 
of potassium sulfate gently ignited. The oxides of silicon and tungsten were separated by the 
method of Perillon as in the analysis of the acid. 


Theory for 
Analysis. Obtained. 4K20.Si02.12W0O3.14H20. 
H,O 7.10% 6.91% (2269, 
S102 1.86% 1.80% 1.73% 
WO; 80.19% 80.38% 80.16% 
K2,0 10.85% 10.91% 10.85% 


Titration of Potassium Salt in Hot Solution.—The potassium salt, in boiling aqueous solu- 
tion, was titrated with standard potassium hydroxide, using phenolphthalein as indicator, in the 
same fashion as the free acid. The solution after the titration was found to yield a dense pre- 
cipitate when strongly acidified with hydrochloric acid. 


Weight of salt 0.7386 gram 0.7420 gram 
Cc. of N/1 KOH consumed 3.695 3.75 

Salt titrated by 1000 cc. V/1 KOH 199 .98 197.8 
Equivalents 17.4 17.6 

Theory 18.0 


This is regarded as further proof of the octabasic character of the acid. 


Preparation and Analysis of the Ammonium Salt.—The ammonium salt was prepared by 
adding a slight excess of ammonium hydroxide to a solution of the acid. The ammonium salt 
was a dense microcrystalline substance, only slightly soluble in water. On ignition of the salt 
the water of crystallization and the ammonia were driven off, leaving silicotungstic anhydride. 
The silica and tungstic anhydride were determined as in the acid. Ammonia was determined by 
distilling the salt with an excess of alkali, receiving the ammonia in standard acid. 


¢ Theory for 
Analysis. Obtained. 4(NHa4)20.Si02.12W0O3.H20. 
H.,0 0.80% 0.938% 0.58% 
(NH,)20 6.69% 6.61% 6.78% 
SiO» 2.00% 1.96% 1.95% 
WO; 90.46% 90 .62% 90.68% 
$102:WO; Leki ZL 1:11.96 ug Be 


Preparation and Analysts of the Alkaloidal Salts.—AIl of the salts, unless other- 
wise specified, were precipitated by addition of a solution of silicotungstic acid to 
a solution of the alkaloidal hydrochloride in hydrochloric acid about 0.6 N. After 


is 


filtration the salts were washed with approximately 1% hydrochloric acid and dried 
at a temperature between 100° and 120°. 

To determine the amount of anhydride present a weighed amount of the salt 
was ignited in an electric muffle. ‘The loss in weight represented alkaloid and water 
of crystallization. In some cases, the composition was further checked by de- 
termining nitrogen according to Kjeldahl. 


Pyridine Silicotungstate.—This is a white microcrystalline powder which is quite soluble 
in hot dilute hydrochloric acid. . 

Analysis. Calculated for 2H:O.Si0..12WO;3.4C;H:N (m. wt. 3196.6): SiOs.12WOs 
88.99%. CsHsN + .-H:0, 11.01%. Found:  $102.12WO;, 89.02%, 89.00%; CsHsN + HO 
10.98%, 11.00%: 

Quinoline Silicotungstate.—This was a white pulverulent substance, apparently less soluble 
than pyridine silicotungstate. 

Analysis. Calculated for 2H20.SiO2.12WO;.4Cy>H;N (m. wt. 3396.7); SiO2.12WOs, 
83.75%. CoH:N + H20, 16.25%. Found: Si02.12WOs;, 83.65%, 83.68%. CoH;N + HO, 
16 Boe l0-32 Ye. 

Nicotine Silicotungstate—Freshly distilled water-white nicotine was quickly dissolved 
in dilute hydrochloric acid and precipitated with an excess of silicotungstic acid. The liquid con- 
taining the amorphous precipitate was heated to boiling and allowed to ‘cool, obtaining a white 
crystalline product, not salmon colored as described by Bertrand (7). 

The product was dried at 60°. 

Analysis. Calculated for 2H20.Si0O2.12WO3.2CioHisN2.5H2O (m. wt. 3294): SiO:.12WOs, 
86.34%; CioHuN2 + H2O, 13.66%. Found: SiOs.12WOs, 86.22%, 86.24%; CioHuN: + H20, 
13.78%, 13:10 %.- 

Another specimen was prepared and dried at 100°. The nicotine used was not water-white 
and the salt had a yellow tint. 

Analysis. Calculated for 2H»:0.5i02.12WO3.2CioHiuN2 (m. wt. 3204): SiO..12WOs, 
88.75%; CioHuN: + HoO, 11.25%. Found: SiO2.12WOs, 88.25%, 88.05%; CioHuNe + H20, 
11.75%, 11.95%. 

Quinine Silicotungstate—This was a white pulverulent compound extremely insoluble in 
water and dilute acids. 

Analysis. Calculated for 2H2,0.SiO2.12WO3.2C2.HasN2O2 (m. wt. 3528.9): SiOe.12WOs, 
80.60%; CooH2aN2O2 + H,0, 19.40%. Found: Si02.12WOs, 80.47%, S012, 5 CsoHosNoO, + 
H.0, 19.53%, 19.49%. 

Cinchonine Silicotungstate—This was a white microcrystalline product extremely insoluble 
in water and dilute acids. ‘The last traces of water of crystallization are removed with difficulty. 
This compound was heated for six hours at 120° without appreciable change. 

Analysis. Calculated for 2H20.SiO2.12WO3.2CisH2N20.2H:0 (m. wt. 3504.9): SiOs.- 
12WOs, SLD... Ci 9H22N20 + HO, 18.85%. Found: SiO». 12WOs, SLID, 81.35%. Cio- 
H»N2,O + H2O, 18.85%, 18.65%. 

Morphine Silicotungstate.—A bufi-colored compound which is moderately soluble in alcohol: 
and dilute acids. 

Analysis. Calculated for 2H2O.SiO2.12WO3.4Ci7HisNO3 (m. wt. 4021.3): Si02.12WOs,, 
70:73:%: Cy7HigNO3 + H:0, ZO N, 37%. Found: SiO2.12WOs, 70.39%, 70.56%; Ci 
H,;NO; + H:O, 29.61%, 29.44%; N, 1.44%. 

Codeine Silicotungstate.—A buff-colored precipitate slightly soluble in alcohol and dilute 
acids. 

Analysis. Calculated for 2H20.SiO2.12WO3.4CisHaNO; (m. wt. 4077.3): SiO2.12WOs, 
69.74%: CisHaiNO; + HO, 30.26%. Found: SiO.12WO3;, 69.51%, 69.65%; CisH»NOs; 
+ HO, 30.49%, 30.35%. 

Apomorphine Silicotungstate—This compound resembled in color and solubility the salts 
of morphine and codeine. 


12 


Analysis. Calculated for 2H:0.Si0O2.12WO3.4Ci7HizNO2 (m. wt. 3949.2): SiOs.12WOs, 
12.02%; Cyi7Hy7NO2 4+ H.0, 27.98%. Found: Si02.12WOs, CZAR 71.94%; Ci7Hi7NOsz, 
27.85%, 28.06%. 

Narceine Silicotungstate—This compound was buff colored when first precipitated. It 
dissolved in hot dilute hydrochloric acid and on cooling was deposited in reddish crystals. 

Analysis. Calculated for 2H:O.SiO2.12WO3.4C2;H2z;NOs (m. wt. 4661.8): SiO..12WOs, 
61.01%; CosHez7NOg + HO, 38.99%; N, 1.20%. Found: S$i0s.12WOs;, 61.14%, 60.97%; 
Co3Hoz,NOs + H20, 38.86%, 39.03%; N, 1.22%. 

Narcotine Silicotungstate—This was a yellowish pulverulent compound, very insoluble in 
water and dilute acid. 

Analysis. Calculated for 2H20.Si0O2.12WO3.4Cs2H»NO;7 (m. wt. 4533.5): SiO2.12WOs, 
62.74%; CoHeaNO7 + HO, 37.26%; N, 1.24%. Found: SiOs.12WOs:, 62.55%, 62.50%; 
CooHo3NO7 a H20O, 31.40%; 37.50%; N, LST. 4 

Strychnine Silicotungstate—This salt was previously prepared by Taigner (loc. cit.). The 
product obtained in this laboratory agrees with the one which he has described. The compound 
was extremely insoluble and required long washing with dilute hydrochloric acid to remove the 
excess of silicotungstic acid. The color was faintly yellow. 

Analysis. Calculated for 2H2O.SiO2.12WO3.4C2:Ha»N2O2 (m. wt. 4217.5): SiO2e.12WOs, 
67.45%; CoHeN2Oe + HO, 32.55%; N, 2.64%. Found: SiO..12WOs, 67.68%, 67.46%; 
C;Ho2N2O2 + H2O, 32.32%, 32.54%; N, 2.46%. 

Brucine Silicotungstate—It had a slight bluish tint and was very insoluble in water and 
dilute acids. Like the strychnine salt long washing was required to remove the excess of silico- 
tungstic acid. 

Analysis. Calculated for 2H:O.SiO2.12WO3.4Co3H2sN204 (m. wt. 4457.9): SiO2.12WOs, 
63.82%; Co3Hop N20. + HO, 36.18%. Found: SiO2.12WOs, 63.56 Zoy.0.04 Yon CosHoeN2Ou > 
H.0, 36.44%, 36.33%. 

Cocaine Silicotungstate—A white microcrystalline salt, already mentioned by Taigner 
(loc. ctt.). 

Analysis. Calculated for 2H2O.Si0O2.12W0O;3.4Ci7H2NO,. (m. wt. 4093.5). SiOQ2.12WOs, 
69.60%; C,7HuNOs, + H.O, 30.40%. Found: Si02.12WOs, 69.80%, 69.70%; Ci7He NO, 
+ H.O, 30.20%, 30.30%. 

Caffeine Silicotungstate—This first precipitated as a white amorphous compound but 
changed to pale yellow crystals on standing. 

Analysis. Calculated for 2H2O.SiO:.12WO3.4CsHi9N.O2 (m. wt. 3657): SiO».12WOs, 
LABS: CsHi9N4O2 + HO, Pa LES Found: SiO2.12WOs, 77.60%, 11.00%; CsgHi9N102 + 
H.O, 22.40%, 22.50%. 

Theobromine Silicotungstate—This formed as a faint yellow powder. 

Analysis. Calculated for 2H20.Si0O..12WO;.4C;HsN.O2 (m. wt. 3600.8): SiOc.12WOs, 
78.99%; CyHsN,0O. + HO, 21.01%; N, 6.28%. Found: SiOc.12WO;, 78.77%, 78.84%; Cr- 
HsN.O2 + HO, 21.28%, 21.16%; N, 6.10%. . 

Veratrine Silicotungstate—The compound had a slight purple color, which was deepened 
by heating in dilute sulphuric acid. A discrepancy existed between the composition as deter- 
mined by theory and analysis. ‘The salt was prepared from several different lots of alkaloid with 
invariably the same composition. Heiduschka and Wolff (17) state that the 1:4 compound could 
only be obtained by precipitation in alcoholic solution. 

Analysis. Calculated for 2H2O.SiO2.12WO3.4C32HsgNO g (m. wt. 5246.5): SiO2.12WOs, 
54.22%; CzeHagNOg + HO, 45.78%. Found: $i02.12WOs, DD.DOUe ODD Loe. Cz3eHsgNOg + 
H20, 44.45%, 44.49%. 

Colchicine Silicotungstate.—This was a bright yellow amorphous salt. 


Analysis. Calculated for 2H20.Si0O2.12W O3.4Co2HosN Oe (m. wt. 44773): SiO». 12WO3, 
63.58%; CoHosNOs + HO, 36.47%; N, 1.25%. Found: SiOv12WO;, 63.55%, 63.45%; 
CooHosNOs + H20, 36.45%, 36.55%; N, 1.21%. 


13 


Jensen (23) claims to have prepared a salt in which the ratio of acid to base was 1:5. 


Atropine Silicotungstate.—This salt was also prepared by Taigner (loc. cit.). It is a white 
crystalline compound, slightly soluble in hot dilute hydrochloric acid. The solubility, however, 
is slight enough to permit of quantitative precipitation from a concentrated solution. 

Analysis. Calculated for 2H20.Si02.12W0O3.4C;7H2NO3 (m. wt. 4037.4): SiOs.12WOs, 
70.45%; CizHesNOs + H:O, 29.55%; N, 1.89%. Found: $102.12WOs, 70.05%, 70.23%; 
Ci7Ha3NO3; + H:20, 29.95%, 29.77%; N, 1.46%. 


Hyoscyamine Silicotungstate.—Like the atropine salt, this compound was white, crystal- 
line and moderately soluble. 


Analysis. Calculated for 2H20.Si02.12WO3.4Ci7HasNO3 (m. wt. 4037.4): SiO2.12WOs, 
70.45%; CizHesNO3; + HO, 29.55%; N, 1.89%. Found: SiOe.12WOs, 70.84%, 70.47%; 
Ci7He3NO3 + H,0O, 29.66%, 20.93%: N, L330 %, 


Berberine Silicotungstate—This was a saffron-colored compound. Pictet (24) gives 
CooHy7NO, as the composition of berberine; Schmidt (25), CooHisNOs. Schmidt’s formula 
was used in the following calculations. 


Analysis. Calculated for 2H2O.Si02.12WO3;.4C2oHisNOs (m. wt. 4293): SiO2.12WOs, 
66.25%; CooHisNOs + H20, 33.75%; N, 1.31%. Found: SiO..12WO3,-66.00%, 66.06%; 
CooHisNOs + H20, 34.00%, 33.94%; N, 1.27%. 


Hydrastine Silicotungstate-—This was a pale yellow amorphous compound. 


Analysis. Calculated for 2H20.Si02.12WO3.4Cs:;H2NOs (m. wt. 4413.4): SiOs.12WOs, 
64.45%; CoHauNOs + H20, 35.55%; N, 1.27%. Found: SiOe.12WOs, 64.27%, 64.20%; 
CoHaNO,. + H20, 35.78%, 35.80%; N, 1.25%. 


SUMMARY. 


1. Silicoduodecitungstic acid has been prepared in a much more stable form 
than previously known by a simplification of a method devised by Copaux. 

2. ‘The acid was found to have the empirical formula 4H2O.Si02.12W0O3.5H20. 
The acid formed normal salts with potassium and ammonium in which eight 
atoms of hydrogen were replaced by a base. 

3. A difference in the degree of ionization of the acid hydrogens was observed. 
in that titrations of the acid by means of a base with methyl orange or methyl] red 
as indicator show a sharp endpoint when four of these hydrogens have been re- 
placed. 

4. ‘The acid forms stable salts with tertiary organic bases. ‘The salts of a 
large number of alkaloids have been prepared, the majority of which are so in- 
soluble as to indicate the possibility of employing them in a quantitative procedure. 

5. The salts of the tertiary bases, precipitated from acid solution, show a 
partial dehydration of the same order as that existing in a dichromate. 

6. All of the phases of this investigation are being continued. 


BIBLIOGRAPHY. 
1. Marignac, Ann. chim. phys., III, 69, 6. Bertrand, Bull. soc. chim., III, 21, 434, 
5, 1863. 1899. 
2. Ibid., IV, 3, 5 (1864). 7. Bertrand, Compt. rend., 128, 742, 1899. 
3. Wyrouboff, Bull. soc. franc. mineral., 8. Bertrand and Javillier, Ann. chim. 
19, 219, 1896. anal. et chim. appl., 14, 165, 1909; Bull, 
4. Copaux, Bull. soc. chim., IV, 3, 101, — Soc. chim., IV, 5, 241, 1909. 
1908. 9. Bertrand and Javillier, Anal. chim. 
5. Goddefroy, Tagebl. d. 49 Naturf. anal. et chim. appl., 16, 251, 1911. 
Vers., (1876). Beilage, 83, through Chem. 10. Javillier, Bull. sci. pharmacol., 17, 


centr., III, 7, 809, 1876. 315, 629, 1910. 


14 


11. Jbid., 19, 70, 1912. 18. Sindlinger and Mach, Zezt. f. angew. 
12. Guillemard, Compt. rend., 132, 1488, Chem., 37, 89, 1924. 
1901. 19. Copaux, Bull. soc. chim., IV, 13, 324, 1913. 
13. Chapin, U. S. Bureau of Animal Ind., 20. Rosenheim and Jaenicke, Zeit. f. 
Bull. 183 (1911). anorg. Chem., 101, 241, 1917. ‘ 
14. Ferenz and David, Pharm. Puost., 47, 21. Perillon, Bull. soc. ind. min. (1884); 
559, 1914. Treadwell-Hall, ‘Analytical Chemistry,” John 
15. Rasmusson, Ber, d. deutsch. pharm. Wiley and Sons, 6th ed., H, 277 (1924). 
Ges., 27, 198, 1917. 22. Jensen, Pharm. Jour., 90, 658, 1918. 
16. Taigner, Zezt. f. anal. Chem., 38, 346, 23. Pictet-Biddle, ‘Vegetable Alkaloids,”’ 
1919. John Wiley and Sons, p. 321 (1904). 
17. Heiduschka and Wolff, Schweiz. A poth. 24. Schmidt, Pharmaceutische Chemie, Fried. 
Zeil.. OS) ala eLoae. Vieweg and Sohn, Vol. II, Part 2, 1750, 1923. 


Il. THE USE OF THE ACID AS A VOLUMETRIC REAGENT FOR 
ALKALOIDS. 


HISTORICAL. 


In a preceding paper (1) the authors have described the method of prepara- 
tion of silicoduodecitungstic acid by a simple and convenient method which yields. 
a product of very definite and stable character. This acid, as prepared by the 
authors, was found to have the composition 4H»2O.SiO2.12WO3.5H2,O. ‘The com- 
position of the normal potassium and ammonium salts was determined, as well as 
the composition of the salts formed by this acid with alkaloids in hydrochloric acid 
solution. For the sake of convenience, the acid will be referred to in this article 
as silicotungstic acid. 

Goddefroy (2) was the first to call attention to the insolubility of alkaloidal 
silicotungstates. Bertrand later (3) published the results of a series of investiga- 
tions, claiming that the work of Goddefroy was unknown to him at the time the 
work was begun, and alone (4) and with Javillier (5) he studied in detail the proper- 
ties of salts of this type applying the acid in the quantitative precipitation of nico- 
tine. Javillier (6) continued the study on the salts of coniine, atropine, sparteine, 
antipyrine, and pyramidone. 

The first direct gravimetric method was described by Chapin (7), in which 
nicotine was precipitated from tobacco extracts and the precipitate ignited, the 
anhydride of the acid being weighed. Ferenz and David (8) used the acid for the 
qualitative detection of alkaloids; Rasmusson (9) determined atropine gravi- 
metrically, applying a correction for the solubility of the atropine salt. Taigner 
(10), working with atropine, cocaine, and strychnine, found that all of their salts 
had the same general type formula, which has been confirmed by the authors 
for all of the monacid tertiary bases studied. Heiduschka and Wolff (11) have 
studied the proper conditions for the formation of the alkaloidal salts and Sind- 
linger and Mach have described a method for the determination of pyridine and 
nicotine in mixtures. 

The authors, in their previous paper (loc. cit.), have shown that for the mon- 
acid tertiary bases, the salts have the type formula 4Alkaloid, 2H2O.SiO2.12WOs, 
and for the diacid tertiary bases, the type formula 2Alkaloid, 2H,O.SiO2.12W0Os3. 
They have also shown that towards methyl orange and methyl red the acid, in its 
neutralizing power towards inorganic bases, is tetrabasic. 


15 


THEORETICAL AND EXPERIMENTAL. 


The usual methods for the quantitative determination of alkaloids in vegetable 
drugs or their preparations involve the separation of the alkaloid by the so-called 
“‘shaking-out process.” In this procedure, advantage is taken of the solubility 
of the alkaloidal salts in water and of the free bases in the organic solvents which 
are immiscible with water. Following the purification of the alkaloid, it is de- 
termined quantitatively by evaporation of the immiscible solvent solution, when 
the residue is weighed, titrated alkalimetrically, or titrated with a standard solu- 
tion of one of the alkaloidal precipitants such as potassium-mercuric iodide or io- 
dine-potassium iodide. 

Beal and Lewis (13) and Beal and Hamilton (14) have reviewed the literature 
of the “‘shaking-out”’ process, calling attention to the sources of error therein and 
have established optimum conditions for these extractions. In this connection 
attention was called to the fact that the number of extractions required for com- 
plete removal of alkaloid from either the aqueous or organic solvent phase of a 
system could not be calculated directly from the simple coefficient of distribution 
which would assume the absence of acid salts or hydrates of a base. They have 
also cited the experience of other investigators, together with their own, in which 
the difficulty of avoiding decomposition of the alkaloidal residue during the final: 
removal of the solvent, especially chloroform, is shown. 

In the alkalimetric determination of alkaloids, difficulty is experienced in the 
selection of a suitable indicator, since the alkaloids are not only weak bases but 
vary widely in their degree of basicity. McGill (15) and others have recently 
met with some success in the application of the hydrogen electrode and other 
methods of electrometric titration to these determinations. 

Gordin (16) has precipitated various alkaloids from a solution containing a 
known volume of standard hydrochloric acid by means of a neutral reagent such 
as iodine-potassium iodide or potassium-mercuric iodide, finding that an equivalent 
quantity of acid is carried down by the precipitate. He, therefore, titrated acidi- 
metrically the excess of the standard acid in the filtrate from this precipitate. This 
method was further studied by Kippenberger (17). Heikel (18) precipitated various 
alkaloids with a standard solution of potassium-mercuric iodide, determining the ex- 
cess of reagent in the filtrate by titration with potassium cyanide and silver nitrate. 

There are at least two objections to these last methods. ‘The methods have, 
in the first place, the usual disadvantages attendant upon quantitative filtration 
and back titration. It is also an established fact that the greater number of alka- 
loidal precipitates of this character begin to decompose after a short time, with 
the accompanying liberation of iodine. 

The contribution of the authors of this paper to the gravimetric determination 
of alkaloids has been in the way of standardizing the method of preparing silico- 
tungstic acid and determining in some additional salts the constancy of their 
composition. ‘They have attempted to devise a rapid volumetric method for gen- 
eral application in the determination of alkaloids which would as far as possible 
be independent of the degree of ionization of the base and upon which moderate 
variations in hydrogen-ion concentration would be without effect.. The manner 
of formation of the alkaloidal silicotungstates suggested the possibility of a volu- 
metric precipitation method. 


16 


Heiduschka and Wolff (loc. cit.) added an excess of a standard solution of 
silicotungstic acid to the alcoholic solution of the alkaloid, filtered off the pre- 
cipitate so formed and determined the excess of the acid by titration with alkali. 
The majority of the alkaloidal silicotungstates are best precipitated from a rather 
strongly acid solution. ‘The authors have therefore made a search for an indicator 
which will show the presence of an excess of silicotungstic acid in a solution. 

Because of the fact that derivatives of tungstic acid may be reduced with the 
formation of lower oxides of tungsten having a blue color, attempts were at first 
made to use as an indicator a strong reducing agent such as titanous chloride or 
colorless ammonium sulphide. The solution of titanous chloride showed some prom- 
ise. It cannot be used as an inside indicator since it will reduce even the pre- 
cipitated silicotungstate. There is also some difficulty in the preservation of the 
reagent. As an outside indicator the results are fairly satisfactory, the end-point, 
a blue color, being rather faint. ‘The ammonium sulphide could not be used with 
the acid solution in which precipitation took place. 

The leuco bases of some blue or green dyestuffs, such as reduced malachite 
green and methylene blue, were next tried, with the idea that the color of the re- 
developed dye would reinforce the color of the tungsten blue. Again only moderate 
success was met with, the endpoint being rather faint and the solutions of the leuco 
bases being very unstable in the presence of atmospheric oxygen. 

When malachite green is dissolved in hydrochloric acid of moderate concen- 
tration, the solution instead of being bluish green in color has a tone which is a 
shade of reddish or brownish orange. ‘The characteristic color of the dye is restored 
upon dilution with a large amount of water, but one drop of 0.01 molar silico- 
tungstic acid in 200 cc. of 0.6 normal hydrochloric acid will at once restore the color | 
of the indicator when one drop of each solution is placed on a porcelain test plate 
and the drops mixed. ‘The best range of acidity for the proper behavior of the 
indicator lies between 0.25 and 1.5 normal hydrochloric acid. 


Preparation of the Indicator—Two grams of malachite green was dissolved in 300 cc. of 
6 N hydrochloric acid. 

Standardization of Silicotungstic Acid.—The molecular weight of the acid is 3006.—An 
approximately 0.01 molar solution was prepared by dissolving 30 grams of the acid in enough water 
to make 1000 cc. of solution. A known amount of pure cinchonine was dissolved in 200 cc. of 
0.6 normal hydrochloric acid and the solution titrated with silicotungstic acid. After allowing 
the precipitate to settle, a drop of the clear supernatant liquid was removed to a spot plate by 
means of a glass tube having an internal diameter of 3 mm. A drop of the indicator solution 
was then added to this by means of a platinum wire loop of 1.5 to 2 mm. diameter, and the two 
drops mixed. While the alkaloid was present in solution the color of the mixed drops was deep 
yellow. With silicotungstic acid in excess the color was bluish green. 

An endpoint with methyl red is obtained when four hydrogens of the acid have been 
neutralized. The acid solution was also standardized by titration with standard sodium hydrox- 
ide, using methyl red as the indicator. 

The solution of the acid may also be standardized by evaporating a definite volume to dry- 
ness, igniting the residue and weighing the silicotungstic anhydride formed. 

Volumetric Assay of Cinchona Bark.—The method used for the extraction of the mixed 
alkaloids was that proposed by Scoville (19) for the Tenth Revision of the United States Pharma- 
copeeia. Five grams of powdered cinchona bark were placed in a 250-cc. flask with 15 cc. of water 
and 5 cc. of hydrochloric acid. After mixing, the contents were digested for 2 hours on the steam- 
bath, then cooled and 200 cc. of a mixture of 3 volumes of ether and 1 volume of chloroform added, 
and after thorough shaking 10 cc. of ammonia water. ‘The mixture was then shaken frequently 


7 


during a period of 12 hours. After the drug had settled, 160 oc. of clear, supernatant liquid were 
decanted into a separatory funnel and repeatedly shaken/out with 2 normal sulphuric acid. ‘The 
combined acid extracts were made alkaline with ammonia ant shalveti/gut with chloroform to 
complete extraction. The chloroform extract was drawn off thréugh a small filter into a beaker 
and the chloroform evaporated on the steam-bath, expelling the last’ traces by means of alcohol. 

Instead of weighing the alkaloidal residue it was softened with alcohol and dissolved in a 
measured volume of 0.1 normal sulphuric acid, and the excess of acid determined by titration with 
0.02 normal sodium hydroxide solution, using methyl red as indicator. 

Following the alkalimetric titration the solution was diluted to a volume of 200 cc. and 20 
ec. of 6 normal hydrochloric acid added. The solution was then titrated with approximately 
0.01 molar silicotungstic acid, using the same procedure as in standardizing against cinchonine, 
with malachite green hydrochloride as the indicator. In both the alkalimetric and silicotungstic 
acid titrations the value 309 was used as the average molecular weight of the mixed anhydrous 
alkaloids. , The principal alkaloids of cinchona contain two atoms of tertiary nitrogen, but the 
basicity of one of these is so slight that in the ordinary alkalimetric titrations the alkaloids are 
regarded as monobasic. Silicotungstic acid, however, reacts with both nitrogen atoms of these 
alkaloids. 


TABLE TI. 
RESULTS OF THE ASSAY OF CINCHONA BARK. 
Titration with 


H2S0s titration, 4H20.Si0O2.12WOs, 
No. Per cent. Per cent. 

i aa) 5.85 
7 in aes ‘es 
3 592 5.60 
4 Di OW, 5 Ay. 
5 Der 610) 
6 Derb 5.68 

Ave. Dee 5.64 


Volumetric Determination of Cinchona Alkaloids without Purification—Ob- 
viously the original ether-chloroform extract of cinchona bark is unsuitable for the 
direct gravimetric determination of total alkaloids because of the presence of non- 
alkaloidal extractives and ammonia. ‘The presence of this ammonia also makes it 
impossible to extract the mixed alkaloids by shaking out with measured volumes. 
of standard acid, afterwards determining the excess of acid by titration. However, 
ammonium salts do not precipitate our reagent in acid solution and the ether- 
chloroform extraction followed by a shaking-out with sulphuric acid should give a. 
protein-free solution. It, therefore, seemed possible to save much time and ob- 
viate a source of error by making a direct titration with silicotungstic acid in the 
sulfuric acid solution obtained as a result of the first series of shakings. 


Accordingly in a new series of assays two 80-cc. portions of the ether-chloroform extract 
were withdrawn. One portion was treated according to the full U. S. P. method, the mixed alka- 
loids being weighed, titrated with sulphuric acid and silicotungstic acid. The other portion was 
extracted with 2 normal sulphuric acid, the combined extracts diluted with water to 200 cc. and 
10 cc. of 12 normal hydrochloric acid added. ‘This solution was then titrated with silicotungstic 


acid in the 11sual manner. 


The volume of silicotungstic acid solution used in these titrations averages. 
about 19cc. ‘The volume of standard sulphuric acid actually consumed is only about 
4cc. In spite of the fact that the excess of sulphuric acid is determined by titration 


18 


i a TABLE II. 
Aa 7" Titration with 
SPE Aiea Titration with 4H20.Si02.12WOs 
No. it | Gravimetric. _, H2SO: titration. 4H20.SiOx.12WO3. without purification. 

1 6.690 Lh 5.85 5.90 59079 
2 6.19 5.87 5.85 5.90 
3 6.37 6 .0O 5.95 5.99 
4 5.83 Sn ft 5.68 5.84 
5) 2.91 3.95 5.84 5.89 
6 5.99 5.70 5. .68 5.92 
Ave. 6 .00 5.84 5.82 o.91 


with a much weaker alkali, there is a potential source of error in the measurement of 
the sulfuric acid which is greater than the possible error in the endpoint with the 
silicotungstic acid. 

Various chemists have pointed out a possible source of error in both gravimetric 
and alkalimetric determinations of alkaloids due to the presence of ammonium salts 
in water solution dissolved in the immiscible solvent. On evaporation to dryness 
there is a possibility that the alkaloid, as a non-volatile base, will expel ammonia, 
forming an alkaloidal salt. White spots have frequently been observed in such 
residues which upon examination have proved to be the alkaloidal salt, as chloride 
or sulfate, entirely free from the ammonium radical. This will naturally give 
high results in the gravimetric assay, and, being neutral, will give low results in the 
alkalimetric titration. 

The reaction with silicotungstic acid is independent of the presence of an acid 
forming a soluble salt, and such a form of contamination will not interfere in the 
proposed method of determination. 


Assay of Fluidextract of Cinchona.*—These preparations were assayed according to the 
Scoville modification previously mentioned. Five cc. of the fluidextract were mixed with 5 grams 
of purified sawdust in a 250-cc. flask and carefully dried on the steam-bath. This residue was 
then digested with hydrochloric acid and extracted in the same manner as cinchona bark. The 
chloroform residue was weighed, and titrated with sulphuric acid and sodium hydroxide, and the 
sulphuric acid extract titrated with silicotungstic acid as above. 


TABLE III. 
ASSAY OF FLUIDEXTRACT OF CINCHONA. 


Titration with 


Gravimetric H2S0s, titration 4H20.Si02.12WOs 

Gms. per 100 cc. Gms. per 100 cc. Gms. per. 100 cc. 
Red cinchona 3.41 3.26 3.36 
3.29 3.32 3.39 
Cinchona!/ Usa.P: 3.34 3.21 3.36 


3.39 3.35 3.33 


Assay of Nux Vomica.—This was assayed by the method of the U. S. P. IX, weighing the 
chloroform residue before the alkalimetric titration and titrating these solutions with silico- 
tungstic acid after adding hydrochloric acid to the neutral solution. The sulphuric acid extract 
was also titrated as in the assay of cinchona. 


* Samples of percolates of cinchona and of red cinchona were furnished by Parke, Davis 
and Company through the courtesy of Mr. F. O. Taylor. 


19 
 TaBie IV. i] 
ASSAY OF NUX VOMIGA! } | 


4 isp gy 


: 
I 


} Titration with 


Pane H2SO4 Titration with , 4F1O.Si02.12WOs 
No. Gravimetric. titration. 4H20.Si02.12WQ;/ without purification. 

1 3.08 2.49 3.06 

>” 2 .64 2.09 2.0 

3 2.54 1.85 2.41 

4 2202 2:38 2.88 Re ee 
5 3.56 
6 Boe 
7 3.34 
8 3.40 


Since the titrations with silicotungstic acid gave values which were very much higher than 
those by the alkalimetric method, the silicotungstic acid which had been standardized against 
cinchonine was titrated against pure strychnine and brucine. 


TABLE V. 
Amt. by 
Amt. by H25O4 4H20.SiO2.12WO3 Per cent recovery by 
Wt. alkaloid. titration. titration. 4H20.5i102.12W0Os. 
eaiGd AG. cinchonine “ot ate 0.1018 100.0 
0.2109 Gm. strychnine 0.2080 0.2492 118.1 
0.2066 Gm. strychnine 0.2042 0.2430 he 
Pes Ones oD) oy a blest eC: Re hie. a i 2 Nr Aa 0.2766 133 .4 
OPDet Grim bricines fees chives 0.2715 132 .2 
0.2065 Gm. brucine 0.2070 a a te Mee ght) RL NE oie os aeons 
0.2090 Gm. brucine GR TOON Ma tach ans Sa). tS ol Ol te aR hig 


The apparent result in the brucine titration was 32.8% too high and for strychnine 17.8% too 
high. The average for both was 25.8%. With this correction the average value in the assay 
of the drug became 2.74%, a very fair agreement with the gravimetric assay. 


Assay of Belladonna Leaves —Belladonna leaves in No. 60 powder were extracted according 
to the method of the U. S. P. IX, and the final chloroformic residue weighed and titrated with 
sulphuric acid and sodium hydroxide, using methyl red as indicator. Other portions of the drug 
were analyzed by titrating the sulphuric acid solution with silicotungstic acid before the final 
purification as in the assay of cinchona bark. Because of the solubility of atropine silicotungstate 
in dilute acids (9), the sulphuric acid extract was titrated without dilution with water, and a cor- 
rection of 0.0048 Gm. of atropine per 100 cc. of solution was made. 


TABLE VI. 


ASSAY OF BELLADONNA Root. 


Titration with 
4H20.Si0O2.12WO3 


No. Gravimetric. H2SO, titration. without purification. 
i! 0.410 A re 90 FO La a Te Boe 
2 0.415 Bee Aon wet od ee ORR ela 
oe are ae Tl a) OS ne eis eer 0.420 
et Nae ON eal Ne, Gi yO a rh ss , 0.440 
Oe en A ee EON Pd on hs a Kia 0.445 
a MME at CY RS EA? iro ON ae Yee Se oe 0.445 


Assay of Stramonium Leaves.—Stramonium leaves were assayed in the same manner as the 
belladonna leaves above, determining the total alkaloids volumetrically by the U. 5S. P. process 
and also by titration with silicotungstic acid without the final purification. The same correction 


was applied as in the assay of belladonna leaves. 


20 


uA TaBLE VII. 
. Assay \o#\StRAMONTUM LEAVES. 


4 , Titration with 4H20.Si0O2.12WOs 
\A \ syn Re © 4\ \) HeSOs titration, without final purification. 
No. | Per cent. Per cent. ss 
LSP ee A ae eee 0.456 ; 
De nh SR ASC a i ees See 0.466 
3 OSELOS ah cn'| he OG Sea ee cee fe 
4 FAC ea se ee nc tar ee 


Assay of Hydrastis Root.—Hydrastis root was assayed gravimetrically according to the 
method of the U. S. P. IX, and by silicotungstic acid without the final purification. 
TaBLE VIII. 


ASSAY OF HypRASTIS Root. 
Titration with 4H2O.SiO2e.12WOs 


U. S. P. Gravimetric, without final purification. 
No. Merecent. Per cent. 

1 3.44 

2 3.52 a eo 
3 3.09 
4 3.15 
3) 3,32 
6 3.29 


Realizing the possibility of error due to the solubility of the alkaloidal silicotungstates, 
Nos. 5 and 6 were titrated by adding the silicotungstic acid in excess, allowing the precipitate to 
stand for thirty minutes, then filtering and washing with 1% hydrochloric acid. The excess of 
silicotungstic acid in the filtrate was titrated with a standard solution of cinchonine hydrochloride. 


A Source of Error in the Method of Assay by Aliquot Parts.—In practically all 
of the alkaloidal assays of the U. S. P. IX, the alkaloids are extracted in the free 


TABLE IX. 
Loss BY EVAPORATION OF PROLLIUS SOLUTION IN CINCHONA ASSAYS. 
Weight of flask Weight of flask 
and solution, and solution, 

No. before. after. Loss 
1 324.5 324 .0 0.5 
2 331.5 dol .0 0.5 
3 319.0 318.5 0.5 
4 305.1 304.7 0.4 
3) 320.8 320.8 0.0 
6 312.7 312.4 0.3 
(j 325.4 323 .8 1.6 
8 305.1 304.7 0.4 
9 325 .0 324.5 0.5 

10 310.0 310.0 0.0 

11 326.5 324.8 ier 
Ds 317 .0 317 .0 0.0 
13 311.0 311.0 0.0 

14 316.0 315.0 12.0 

15 305.5 304.5 LEQ) 
16 318.0 315.0 3.0 


Ave. 0.7 Gm. 


state by macerating with some modification of Prollius mixture. F ollowing this 
maceration, the drug is agglutinated, if necessary, by the addition of a small 


21 


amount of water and a definite volume of the non-aqueous solution / decanted. 
The final calculation is based upon the supposed relationship! jof| this poems of 
solution to the volume of liquid with which the drug was originally, macerated. 
Unless perfectly stoppered vessels are used for the maceration, there is ‘inevitably 
some loss of solvent during maceration, an effect which is oftentimes intensified 
by shaking. For this reason we have made it our practice to weigh the extraction 
flask at the beginning of the maceration and just before the removal of the aliquot, 
making up to the original weight if necessary by adding more of the non-aqueous 
solvent. We are of the opinion that the Pharmacopceia should contain a caution- 
ary statement regarding this loss. The foregoing table contains the weights ob- 
tained in a series of extractions of cinchona, the macerations being made in Erlen- 
meyer flasks having well-fitting ground glass stoppers. 


SUMMARY. 


1. Aqueous solutions of silicotungstic acid restore the green color to an orange- 
colored solution of malachite green in hydrochloric acid. 

2. Using the hydrochloric acid solution of malachite green as an outside 
indicator, it has been found possible to titrate alkaloidal salts with standard solu- 
tions of silicotungstic acid in the presence of free hydrochloric or sulphuric acid. 

3. The results so obtained by slightly modifying the U.S. P. assay processes 
compare favorably with those obtained by the official method. 

4. It has been found possible to materially shorten the official methods by 
titrating the first sulphuric acid extract with silicotungstic acid. 

5. Attention is called to the possibility of losses of solvent in the initial ex- 
traction of the drug in the official assay processes. 

6. A further study is being made of the possibilities of this reagent in the 
volumetric determination of alkaloids. 


BIBLIOGRAPHY. 


1. North and Beal, Jour A. Pu. A., pre- 10. Taigner, Zeit. anal. Chem., 58, 346, 
vious article. 1919. 

2. Goddefroy, Tagebl. d. 49 naturf. wissen., 11. _Heiduschka and Wolff, Schweiz. A poth. 
p. 83 (1876). Leite, -58,- 2191920. 

3. Bertrand, Bull. soc. chim., (III) 21, 12. Sindlinger and Mach, Zeit. angew. 
434, 1899. 89, 1924. 


4. Bertrand, Compt. rend., 128, 742, 1899. 

5. Bertrand and Javillier, Ann. chim. 
Gui 145 16550909 16;4251, 1911; Bull. 
-soc. chim., (IV), 5, 241, 1909. 

6. Ujavillier, ~ Bull, set. 
315, 629, 1910; 19, 70, 1912. 

7. Chapin, U. S. Bur. Animal Ind., Bull. 
133 (1911). 

8. Ferenz 
47, 559, 1914. 

9. Rasmusson, Ber. 
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URBANA, ILLINOIS, 
AvucustT, 1924. 


pharmacol., 17, 


and David, Pharm. 


d. deutsch. pharm. 


Chem., 37, 


Jost 


13. ° Beal and Lewis, Jour. A. PH: A., 5, 
812, 1916. 

14. Beal and Hamilton, Jour. A. Pu. A., 
9, 9, 1920. 

15. McGill, 
PMS oat AS Vopr 

16. Gordin, Ber., 32, 2871, 1899. 


Jour. Am. Chem. Soc., 44, 


17. Kippenberger, Zeit. anal. Chem., 42, 
101, 1908. 
18. Heikel, Chem. Zeit., 32, 1149, 1908. 


19. Scoville, Jour. A. Pu. A., 9, 867, 1920. 


VITA 


Edward Oscar North was born October 29, 1895, in Rockford, Illinois. His 
early training was received in the Rockford schools. In 1914 he entered Beloit 
College where he was graduated in 1918 with the degree of Bachelor of Science. 
In 1922 he received the degree of Master of Science from the University of Llinois. 
He has held the following positions: 

Assistant in Chemistry, Beloit College, 1918-1919. 

Instructor in Chemistry, Beloit College, 1919-1920. 

Assistant in Chemistry, University of Illinois, 1920-1924. 

He is a member of Sigma Xi and Phi Lambda Upsilon. 


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